S-nitrosylated compounds are compounds with one or more —S—NO groups. An —S—NO group is also referred to in the art as a sulfonyl nitrite, a thionitrous acid ester, an S-nitrosothiol or a thionitrite.
Various S-nitrosylated species are known and include:    a) Certain S-nitrosylated polysaccharides, such as S-nitrosylated starch, cellulose, alginic acid, K-carrageenan, fucoidin, and cyclodextrins (e.g., α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin).    b) Certain lipoproteins substituted at the S-moiety with a nitric oxide moiety. Examples are chylomicron, a chylomicron remnant particle, a very low-density lipoprotein, a low-density lipoprotein, an intermediate-density lipoprotein, a high-density lipoprotein and a lipoprotein (a).    c) Certain S-nitrosylated polypeptides and proteins, such as neuropeptides, tissue-type plasminogen activator, streptokinase, urokinase, BSA, immunoglobulin (e.g., IgG, IgM, IgA, IgD, IgE), hemoglobin, myoglobin and cathepsin.    d) Certain S-nitroso amino acids and their derivatives (many of which are ACE inhibitors) including S-nitroso-N-acetylcysteine, S-nitroso-glutathione, S-nitrosocysteine, S-nitroso-gamma-methyl-L-homocysteine, S-nitroso-L-homocysteine, S-nitroso-gamma-thio-L-leucine, S-nitroso-delta-thio-L-leucine, S-nitroso-captopril, N-acetyl-S-nitroso-D-cysteinyl-L-proline, N-acetyl-S-nitroso-D, L-cysteinyl-L-proline, 1-[5-guanidino-2-(S-nitroso)mercaptomethyl-pentanoyl]-L-proline, 1-[5-amino-2-(S-nitroso) mercaptomethyl-pentanoyl]-4-hydroxy-L-proline, 1-[5-guanidino-2-(S-nitroso)mercaptomethyl-pentanoyl]-4-hydroxy-L-proline, 1-[2-aminomethyl-3(S-nitroso)-mercaptomethyl-pentanoyl]-L-proline, and S-nitroso-L-cysteinyl-L-proline.    e) Certain other S-nitrosylated compounds such as S-nitroso-penicillamine, S-nitroso-N-acetylpenicillamine, and Y(CH2)xSNO, where x is 2-20 and Y can be —H, —SH, fluoro, C1-C6 alkoxy, cyano, carboxamido, C3-C6 cycloalkyl, aralkoxy, C2-C6 alkylsulfinyl, arylthio, C1-C6 alkylamino, C2-C15 dialkylamino, hydroxy, carbamoyl, C1-C6 N-alkylcarbamoyl, C2-C15 N,N-dialkylcarbamoyl, amino, hydroxyl, carboxyl, hydrogen, nitro or aryl; wherein aryl includes benzyl, naphthyl, and anthracenyl groups.
Several of these S-nitrosothiol species have been noted for their platelet inhibition and/or thrombolytic characteristics, as well as their ability to relax skeletal muscle and smooth muscle, including vascular smooth muscle (vasodilation), airway smooth muscle, gastrointestinal smooth muscle, corpus cavernosum smooth muscle, bladder smooth muscle, and uterine smooth muscle. For additional information, see, e.g., U.S. Pat. No. 5,770,645, U.S. Pat. No. 5,583,101, U.S. Pat. No. 5,863,890, U.S. Pat. No. 5,612,314, U.S. Pat. No. 5,648,393, U.S. Pat. No. 6,057,367 or U.S. Pat. No. 5,380,758, U.S. Pat. No. 5,593,876, U.S. Pat. No. 5,574,068 or U.S. Pat. No. 5,385,937, the disclosures of which are hereby incorporated by reference in their entireties.
U.S. Pat. No. 5,770,645, the entire disclosure of which is incorporated by reference immediately above, teaches that compounds with one or more free nucleophilic groups, such as polysaccharides that have been provided with pendant thiol groups, can be reacted with a nitrosylating agent under conditions suitable for nitrosylating the free thiol groups. Nitrosylating agents disclosed as suitable include acidic nitrite, nitrosyl chloride, compounds comprising an S-nitroso group (S-nitroso-N-acetyl-D,L-penicillamine (SNAP), S-nitrosoglutathione (SNOG), N-acetyl-S-nitrosopenicillaminyl-S-nitrosopenicillamine, S-nitrosocysteine, S-nitrosothioglycerol, S-nitrosodithiothreitol and S-nitrosomercaptoethanol), an organic nitrite (e.g. ethyl nitrite, isobutyl nitrite, and amyl nitrite), peroxynitrites, nitrosonium salts (e.g. nitrosyl hydrogen sulfate), oxadiazoles (e.g. 4-phenyl-3-furoxancarbonitrile) and the like. For more information, see U.S. Pat. No. 5,770,645.